Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Biomolecules. 2023 Jul 31;13(8):1194. doi: 10.3390/biom13081194.
Lymphocyte function-associated antigen-1 (LFA-1) and its endothelial ligand intercellular adhesion molecule-1 (ICAM-1) are important for the migration of lymphocytes from blood vessels into lymph nodes. However, it is largely unknown whether these molecules mediate the homeostatic migration of lymphocytes from peripheral tissues into lymph nodes through lymphatic vessels. In this study, we find that, in naive mice, ICAM-1 is expressed on the sinus endothelia of lymph nodes, but not on the lymphatic vessels of peripheral tissues. In in vivo lymphocyte migration assays, memory CD4 T cells migrated to lymph nodes from peripheral tissues much more efficiently than from blood vessels, as compared to naive CD4 T cells. Moreover, ICAM-1 deficiency in host mice significantly inhibited the migration of adoptively transferred wild-type donor lymphocytes from peripheral tissues, but not from blood vessels, into lymph nodes. The migration of LFA-1-deficient donor lymphocytes from peripheral tissues into the lymph nodes of wild-type host mice was also significantly reduced as compared to wild-type donor lymphocytes. Furthermore, the number of memory T cells in lymph nodes was significantly reduced in the absence of ICAM-1 or LFA-1. Thus, our study extends the functions of the LFA-1/ICAM-1 adhesion pathway, indicating its novel role in controlling the homeostatic migration of lymphocytes from peripheral tissues into lymph nodes and maintaining memory T cellularity in lymph nodes.
淋巴细胞功能相关抗原-1（LFA-1）及其内皮配体细胞间黏附分子-1（ICAM-1）对于淋巴细胞从血管迁移到淋巴结至关重要。然而，这些分子是否介导淋巴细胞从外周组织经淋巴管归巢迁移到淋巴结，在很大程度上仍不清楚。在这项研究中，我们发现，在未致敏的小鼠中，ICAM-1 仅在淋巴结的窦内皮细胞上表达，而不在外周组织的淋巴管上表达。在体内淋巴细胞迁移实验中，与初始 CD4 T 细胞相比，记忆 CD4 T 细胞从外周组织迁移到淋巴结的效率更高。此外，宿主小鼠中 ICAM-1 的缺失显著抑制了从外周组织而非血管中过继转移的野生型供体淋巴细胞向淋巴结的迁移。与野生型供体淋巴细胞相比，LFA-1 缺陷型供体淋巴细胞从外周组织向野生型宿主小鼠淋巴结的迁移也显著减少。此外，在缺乏 ICAM-1 或 LFA-1 的情况下，淋巴结中的记忆 T 细胞数量显著减少。因此，我们的研究扩展了 LFA-1/ICAM-1 黏附途径的功能，表明其在控制外周组织中淋巴细胞归巢迁移和维持淋巴结中记忆 T 细胞数量方面具有新的作用。
